This invention is related to the field of chemistry, and particularly to solution phase chemistry. More specifically, the invention relates to chemical constructs that may be used with solution phase chemistries.
Modern chemistry is a mature discipline that utilizes a variety of procedures. For example, one common procedure is the reaction of various components under suitable conditions to produce one or more products. Another procedure is the protection of potentially labile functionality present in the material prior to carrying out a reaction or process on the material. A further procedure is the separation of wanted materials from unwanted materials, either after a reaction or from complex raw materials. Still another procedure is the identification of one or more of the components present after carrying out a reaction, or of the components of a solution of raw materials. Yet another procedure is the quantitation or measurement of the relative or absolute amount of materials of one or more of the components of a solution.
The choice of a particular procedure often depends on the properties of the material in question. For example, the material may be non-charged, making accurate detection by mass spectroscopy difficult, if not impossible. As another example, if the material is a poor chromophore, spectroscopic monitoring of the material throughout a process may be impractical. As still another example, if a desired material has properties similar to other components in a solution, separation of the desired material from the other components may be difficult.
It is also often the case that because of the difficult and time-consuming nature of the separation and/or purification steps required to produce an acceptable quality of reaction product, large molar excesses of one or more of the reactants is avoided. The addition of large molar excesses to drive a reaction to completion by the law of mass action is well known to chemists and extensively used when chemistry is carried out on a solid-phase. Therefore by an enhancement of the ability to purify or separate a reaction product from other reaction components, larger excesses of reactants or reagents, to drive reactions to completion, could be used more often when carrying out chemistries in solution-phase.
Hence, even though modern chemistry is a mature discipline, improvements to such procedures are continually sought. Hence, this invention is related to techniques for improving one or more of the above procedures, among others.
The invention provides chemical constructs for solution phase chemistries to facilitate the separation, identification and/or quantitation of a chemical component or material. In one embodiment, such a chemical construct comprises a module having a reversible attachment unit that permits the module to be reversibly attached to the chemical component. The module further includes one or more attribute conferring units, such as separation attribute conferring units, identification attribute conferring units, and quantitation attribute conferring units. Such attribute conferring units may be used in any number or combination. In one aspect, the reversible attachment unit comprises a chemical functionality that is chemically attachable to a chemical component in a solution in such a way that the chemical component may be removed from the attachment unit in a subsequent chemical step while the chemical component remains unchanged or changed to another chemical component of utility.
A wide variety of separation attribute conferring units may be used. For example, the separation attribute-conferring unit may be configured to differentially precipitate the chemical component/construct combination away from other materials in the solution. Alternatively, the separation attribute-conferring unit may be configured to differentially crystallize the chemical component/construct separately from other materials in the solution. As another example, the separation attribute-conferring unit may comprise a charged group to facilitate the separation of the chemical component/construct differentially from non-charged materials in the solution when used with ion exchange chromatography. As still another example, the separation attribute-conferring unit may be sized to make the chemical component/construct larger in size than other components in the solution when used with size exclusion chromatography. In one particular example, the separation attribute conferring unit may comprise an affinity component to provide the chemical component/construct with an affinity for a complementary support that is different than for other components in the solution when used with affinity chromatography. As a further example, the separation attribute-conferring unit may comprise a solubility component to make the chemical component/construct differentially soluble in a particular solvent relative to other components to permit phase extraction separation of the chemical component. As yet another example, the separation attribute conferring unit may comprise a physical characteristic selected to favor separation of the chemical component/construct by a separation process such as thin layer chromatography, two dimensional gel separation, gas chromatography, capillary electrophoresis, membrane separation or the like.
In one particular aspect, the identification attribute-conferring unit may comprise an ionizable chemical group that is adapted to facilitate identification of the chemical component/construct in a mass spectrometer. As an alternative, the identification attribute-conferring unit may comprise an isotopic mass peak splitter to facilitate identification of the chemical component/construct in a mass spectrometer. In another aspect, the identification attribute-conferring unit may comprise a chromophore to permit identification of the chemical component using an optical detector or monitor.
In yet another aspect, the quantitation attribute conferring unit may comprise a reference material that is quantitatively related to the amount of the chemical component. In this way, the amount of chemical component may be determined using a mass spectrometer.
In another embodiment, the invention provides a method for evaluating and/or processing a reaction product contained in a solution. According to the method, a module is reversibly attached to a first chemical component. The module comprises a reversible attachment unit that reversibly attaches the module to the first chemical component, and one or more attribute conferring units, such as separation attribute conferring units, identification attribute conferring units, and quantitation attribute conferring units. The first chemical component is reacted with at least a second chemical component to produce a reaction product. The reaction product may then be separated from any other components in the solution using a separation attribute conferring unit. The reaction product may be identified using an identification attribute conferring unit, and the reaction product may be quantified using a quantitation attribute conferring unit. Hence, the attribute conferring units provide the opportunity to separate, identify and/or quantitate the results of the reaction. At any time in the process, the module may be removed from the reaction product without affecting or changing the reaction product.
One example of a technique that may be used to separate the reaction product from other components in the solution is by precipitating the reaction product in the solution, with the separation attribute conferring unit permitting the reaction product to precipitate differentially from any other components in the solution. As another example, the reaction product may be crystallized, with a separation attribute conferring unit permitting the reaction product to crystallize differentially from any other components in the solution. In another example, the separating step may comprise adding a charge group to the reaction product with a separation attribute conferring unit and separating the reaction product using ion exchange chromatography. As a further example, the separating step may comprise making the reaction product larger in size than the other components in the solution using a separation attribute conferring unit and separating the product using size exclusion chromatography. As still another example, the separating step may comprise providing the reaction product with a certain affinity for a column using the separation attribute conferring unit and separating the reaction product using affinity chromatography. In yet another example, the separating step may comprise providing the reaction product with a certain solubility using a separation attribute conferring unit, and separating the reaction product using reverse chromatography or normal phase chromatography.
In one particular aspect, the reaction product may be identified by ionizing the reaction product using a charged identification attribute conferring unit and placing a sample of the solution in a mass spectrometer. In another aspect, the reaction product may be quantified by using an isotopic mass peak split signature and a reference material that is part of a module. The reaction product is placed into a mass spectrometer and identified by the signature profile produced by the mass spectrometer. The measured signal of the reference material is then compared with the reaction product, and a yield estimated for that product. Alternatively, other techniques that are known in the art may be used to measure the resulting materials, including spectrophotometric methods.